β‐Adrenergic Receptor Activation Modulates the Induction of Complex Spike‐Dependent <scp>LTP</scp> by Regulating Multiple Forms of Heterosynaptic Plasticity

Norepinephrine, acting through β-adrenergic receptors (β-ARs), has a key role in hippocampus-dependent forms of learning. Although β-AR activation also facilitates the induction of Hebbian LTP, recent findings indicate that a non-Hebbian form of synaptic plasticity, known as behavioral timescale synaptic plasticity (BTSP), underlies hippocampus-dependent spatial learning. To explore the role of noradrenergic signaling in BTSP, I investigated the effects of the β-AR activation on complex spike (CS) burst-dependent LTP, a form of BTSP induced by theta-pulse stimulation (TPS) protocols in the CA1 region of mouse hippocampal slices. β-AR activation not only enhanced the homosynaptic potentiation of synaptic transmission induced by TPS but also modulated heterosynaptic forms of plasticity critical for CS burst-dependent LTP induction. Specifically, β-AR activation enhanced the heterosynaptic facilitation of CS bursting induced by brief TPS trains and facilitated the ability of synapses to interact in a cooperative fashion to undergo LTP, even when independent groups of synapses were activated up to 10 s apart. β-AR activation also enhanced a CS burst-dependent form of heterosynaptic depression elicited by longer trains of TPS, resulting in a winner-take-all form of synaptic competition where the β-AR-mediated facilitation of LTP induction at one group of synapses was associated with a strong, heterosynaptic suppression of LTP at other synapses. Together, these findings indicate that β-AR activation dynamically regulates fundamental properties of CS burst-dependent synaptic plasticity by modulating multiple forms of heterosynaptic plasticity.